In search of a necrotic enteritis vaccine

The global poultry industry takes an estimated $6 billion hit every year from necrotic enteritis (NE). Intestinal damage caused by this condition means birds don’t grow well, and current prevention and treatment approaches centre around antibiotics, which are under increasing scrutiny.

“There is a real need globally for an effective necrotic enteritis vaccine,” says John Prescott, professor emeritus with the University of Guelph’s Department of Pathobiology who spent many years working on a vaccine. “We want to prevent necrotic enteritis with ways other than antibiotics and that’s where vaccines come in.”

Canadian researchers have been focused on the pathogen that causes NE – Clostridium perfringens, which is a highly specialized bacterium that adapts to the chicken intestine. They hope to use the bacteria to develop an effective vaccine to protect birds.

Prescott and Joshua Gong, a senior research scientist with Agriculture and Agri-Food Canada, have worked together to understand how C. perfringens develops in hopes of finding effective protection options. They worked on different parts of the pathogen and, ultimately, collaborated on the most promising prospect for an effective NE vaccine for poultry producers. A commercial vaccine could be expected available in as little as three years.

 Gene manipulation falls short
Prescott and his team set out to develop a new oral live bacterial vaccine for NE. He looked for strains of C. perfringens that they could weaken by knocking out key genes. By deleting the selected genes, they hoped to manipulate the pathogen to deliver the desired balance of expressing the antigens that birds would need to develop immunity to the bacterium, without causing any NE damage. In vaccinology terms, a live attenuated vaccine.

The advantage of this approach would be that the vaccine would be inexpensive to produce, easily delivered in water, safe and be effective because it would grow where immunity was needed.

But what they learned in the lab was that they could produce some immunity to NE in chickens using the modified live organism as a vaccine, but it wasn’t going to be an industry solution. “We would have loved to have discovered a strain of the NE-causing bacteria that was effective in preventing NE…but we didn’t,” Prescott says.

“We worked really hard to target specific genes in the bacterium that are important for making the organism grow in the bird’s intestine that could cause immunity and not disease. We didn’t produce any strains of C. perfringens that could produce any significant immune protection for birds against NE without causing any damage.”

Pili provide a promising approach
Around the same time, Joshua Gong and his associate Dion Lepp were looking at the NE vaccine potential of an appendage (pilus) on the surface of C. perfringens at AAFC’s Guelph Research and Development Centre. “John and I had worked together to understand how C. perfringens developed NE, and then we worked on different parts of the bacterium in the search for an NE vaccine,” Gong says.

“In my lab, we were looking at pili, which often attach to the gut of the host to initiate disease, as a route to developing an NE vaccine,” Gong says. This approach has yielded exciting results and a promising prospect for a commercial NE vaccine for Canadian poultry producers.

“We discovered two pilus (Latin for hair) proteins on the pathogen that produced the best antibody response in a vaccine to protect birds against NE,” says Gong, who stresses that Prescott contributed significantly to the development of the pilus vaccine. “We are now patenting these two pilus proteins that hold the best prospect for an effective NE vaccine.”

Gong and Lepp are talking to vaccine companies to collaborate on developing this vaccine to the next step towards commercialization, including exploring the route of administration that is the most feasible.

“I would expect we are about three years away from a commercially available vaccine for poultry producers that will offer effective protection against necrotic enteritis,” says Gong, adding he’s hopeful Canada could be the first market.  

This research was part of the Poultry Science Cluster 2, which was supported by Agriculture and Agri-Food Canada as part of Growing Forward 2, a federal-provincial-territorial initiative. Prescott’s work was also supported by the Ontario Ministry of Agriculture, Food and Rural Affairs, and Gong’s research was also funded by Agriculture and Agri-Food Canada.